Human lymphoreticular malignancies are tumors in which normal developmental sequences have been arrested or otherwise disrupted. Accumulating knowledge of the development and function of lymphocytes provides a basis for understanding these abnormal patterns of differentiation. The development of specific antiserums to T, B and precursor cell differentiation antigens is an important further step in this work. B and T cell lymphoblastoid lines RPMI 8392 and 8402 were chosen as a source from which to identify certain differentiation antigens. These lines were derived from the same leukemic donor, and RPMI 8402 appears to be an outgrowth of the tumor stemline. Using a blocking technique, we developed antiserums in rabbits specific for cell membrane antigens found on only one of the 2 cell lines. This technique reduces the absorptions needed to render the antiserum specific for one cell type. In membrane immunofluorescence tests, antiserum to the B cell line 8392 reacts with about 20% of peripheral blood lymphocytes, 100% of chronic lymphocytic leukemic leukocytes, and the majority of the blast cells from a patient with non-T cell acute lymphoblastic leukemia. Antiserum to the T cell line 8402 reacts with about 80% or peripheral blood lymphocytes, 80% of thymocytes and 100% of the blasts from a patient with T-cell lymphoblastic lymphoma. In future work, we plan to develop higher titer antiserums with the same specificity. These specificities will be defined by immunofluorescence tests, using conventional microscopy and a fluorescence-activated cell sorter. We will establish patterns of reactivity of these serums with mature lymphocytes, differentiating lymphoid and hematopoietic cells and malignant lymphoid cells. The specificities in the serums will then be analyzed by systematic absorption tests. Serums will be absorbed with tonsil lymphocytes and retested on differentiating and neoplastic cell populations. These absorptions will define differentiation or tumor-associated antigens. These serums will be further absorbed with differentiating cell populations, for example thymocytes or fetal liver cells. Tests on neoplastic cells will then be repeated to identify possible tumor-associated antigens. Our goal is to resolve the antiserums into antibodies specific for anigens on mature, differentiating, and neoplastic lymphoid cells.